Vaccines Immunogenicity in Renal, Hepatic, Cardiac or Pulmonary Transplanted Children (COVAGREF)

Vaccines Immunogenicity in Children Transplanted or Candidate for a Renal, Hepatic, Cardiac or Pulmonary Transplantation, Followed in the Rhône-Alpes Region. A Descriptive and Prospective Monocentric Cohort Study

Thanks to improved surgical techniques, postoperative management and immunosuppressive therapies, an increasing number of children benefit from renal, hepatic, cardiac and pulmonary transplantation. Infection is a significant cause of mortality and morbidity in these patients, particularly due to vaccine-preventable diseases. Vaccination is one of the effective means of reducing infection-related mortality in these particularly vulnerable children. It is mostly well-tolerated, but all the more effective as it is performed early before transplantation, at best during a dedicated consultation, according to a vaccine scheme adapted to the immunocompromised child. In the almost constant absence of clinical efficacy data in populations of immunocompromised individuals, vaccine efficacy is most often indirectly estimated by immunogenicity, using protective correlates obtained by extrapolation in immunocompetent individuals.

Primary objective: To estimate the immunogenicity of vaccines recommended in children transplanted or candidate for renal, hepatic, cardiac and pulmonary transplantation, using serological titers measurements before and after a vaccine injection for: influenza, pneumococcus, chicken pox, measles, tetanus, hepatitis A and hepatitis B.

These serological titers will be compared to correlates of protection existing for each valency.

The evolution of serological titers will be described during the first year. The vaccination will be carried out within the routine care, according to the recommendations.

Secondary objectives:

• describe and quantify the vaccination status of patients
• describe the vaccination coverage of their entourage
• evaluate the tolerance and efficacy of vaccines

Study Overview

• Status: Unknown
• Conditions: Transplantation
• Intervention / Treatment: Biological: Recommended vaccine scheme according to French Vaccine Schedule 2015

• Study Type: Interventional
• Enrollment (Anticipated): 341
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69500
    • Recruiting
    • Hospices Civils de Lyon
    • Contact: Laure HEES, MD; Phone Number: +33 427 855 632; Email: laure.hees01@chu-lyon.fr
    • Contact: Behrouz Kassaï, MD; Phone Number: +33 472 357 231; Email: behrouz.kassai-koupai@chu-lyon.fr
    • Principal Investigator: Laure HEES, MD
    • Sub-Investigator: Yves GILLET, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• children and adolescent between 0 and 17 years old
• registered in the database of the Agency of Biomedicine
• transplanted or waiting for a renal, hepatic, cardiac or pulmonary transplantation
• followed up in the Rhône-Alpes region between January 1st , 2015 and December 31th, 2016
• patients requiring vaccination in standard care

Exclusion Criteria:

• adults
• children or adolescent not able not comply with protocol
• children, adolescent or patient parents or legal guardian not opposed to study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patient already transplanted or waiting for a transplantation

Biological: Recommended vaccine scheme according to French Vaccine Schedule 2015; BCG; Measles mumps rubella (MMR); Varicella (chicken pox); Rotavirus; Seasonal flu (live vaccine delivered nasally and inactivated vaccine injectable); Yellow Fever; Diphteria tetanus poliomyelitis whopping cough (DTwP); Haemophilus influenzae type b; Hepatitis B; Meningococcus conjugate; Pneumococcus; Human papillomavirus; Hepatitis A Vaccine administration would be done according to French Vaccine Schedule 2015 for mainstream population and for grafted children or transplant candidate children

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity of vaccines recommended in children transplanted or candidate for renal, hepatic, cardiac and pulmonary transplantation	The immunogenicity is appraised from serological titer before and after vaccine injection. These serological titers will be compared to existing reference protection correlates for each valency, and defined as protective or non-protective: Tetanus (>0,1 UI/ml), hepatitis B (>10 mUI/ml), hepatitis A (> 20 mUI/ml), measles (0,18 in EIA index), chicken pox (> 5 gp Elisa UI/ml or > 50 UI/l with an highly sensitive test), influenza (Hemagglutination Inhibition Assay > 1/40), pneumococcus (0,35 µg/ml, > 0,4 mg/l for each specific serotype, if > 2/3 or 4/6, protecting serotype)	at Month 0
Immunogenicity of vaccines recommended in children transplanted or candidate for renal, hepatic, cardiac and pulmonary transplantation	The immunogenicity is appraised from serological titer before and after vaccine injection. These serological titers will be compared to existing reference protection correlates for each valency, and defined as protective or non-protective: Tetanus (>0,1 UI/ml), hepatitis B (>10 mUI/ml), hepatitis A (> 20 mUI/ml), measles (0,18 in EIA index), chicken pox (> 5 gp Elisa UI/ml or > 50 UI/l with an highly sensitive test), influenza (Hemagglutination Inhibition Assay > 1/40), pneumococcus (0,35 µg/ml, > 0,4 mg/l for each specific serotype, if > 2/3 or 4/6, protecting serotype)	between Month 1 and Month 3
Immunogenicity of vaccines recommended in children transplanted or candidate for renal, hepatic, cardiac and pulmonary transplantation	The immunogenicity is appraised from serological titer before and after vaccine injection. These serological titers will be compared to existing reference protection correlates for each valency, and defined as protective or non-protective: Tetanus (>0,1 UI/ml), hepatitis B (>10 mUI/ml), hepatitis A (> 20 mUI/ml), measles (0,18 in EIA index), chicken pox (> 5 gp Elisa UI/ml or > 50 UI/l with an highly sensitive test), influenza (Hemagglutination Inhibition Assay > 1/40), pneumococcus (0,35 µg/ml, > 0,4 mg/l for each specific serotype, if > 2/3 or 4/6, protecting serotype)	Month 12
Immunogenicity of vaccines recommended in children transplanted or candidate for renal, hepatic, cardiac and pulmonary transplantation	The immunogenicity is appraised from serological titer before and after vaccine injection. These serological titers will be compared to existing reference protection correlates for each valency, and defined as protective or non-protective: Tetanus (>0,1 UI/ml), hepatitis B (>10 mUI/ml), hepatitis A (> 20 mUI/ml), measles (0,18 in EIA index), chicken pox (> 5 gp Elisa UI/ml or > 50 UI/l with an highly sensitive test), influenza (Hemagglutination Inhibition Assay > 1/40), pneumococcus (0,35 µg/ml, > 0,4 mg/l for each specific serotype, if > 2/3 or 4/6, protecting serotype)	3-month post-transplantation (if transplantation occurs during the study)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of blood antibodies corresponding to the following vaccine valencies: influenza, pneumococcus, chicken pox (varicella), measles, tetanus, hepatitis A and hepatitis B.		at Month 0
Levels of blood antibodies corresponding to the following vaccine valencies: influenza, pneumococcus, chicken pox (varicella), measles, tetanus, hepatitis A and hepatitis B.		between Month 1 and Month 3
Levels of blood antibodies corresponding to the following vaccine valencies: influenza, pneumococcus, chicken pox (varicella), measles, tetanus, hepatitis A and hepatitis B.		at Month 12
Levels of blood antibodies corresponding to the following vaccine valencies: influenza, pneumococcus, chicken pox (varicella), measles, tetanus, hepatitis A and hepatitis B.		3-month post-transplantation (if transplantation occurs during the study)
the number of early or late injections	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	at Month 0,
the number of missing injections and supplementary injections	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	at Month 0,
the number of days in advance or delayed from recommended injections (per injection and cumulative)	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	at Month 0,
the number of early or late injections	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	between Month 1 and Month 3
the number of missing injections and supplementary injections	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	between Month 1 and Month 3
the number of days in advance or delayed from recommended injections (per injection and cumulative)	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	between Month 1 and Month 3
the number of early or late injections	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	at Month 12
the number of missing injections and supplementary injections	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	at Month 12
the number of days in advance or delayed from recommended injections (per injection and cumulative)	Vaccine status compliance with vaccine recommendation, from literature data and from the opinion of the Vaccine Technical Committee President. Compliance will be appraised by considering for each valence: the number of early or late injections; the number of missing injections and supplementary injections; the number of days in advance or delayed from recommended injections (per injection and cumulative) 2 age groups will be differentiate : <2 years (primary vaccination) and >2 years For each age group, early or late injections are defined by considering literature data and the opinion of the Vaccine Technical Committee President.	at Month 12
Vaccination coverage of patients' entourage	Number of missing, additional, early or late injections, compared to vaccine recommendations.	at month 0
Patients' vaccine tolerance	Local reactions, fever, clinical or biological signs of rejection	at Week 1
Patients' vaccine tolerance	Local reactions, fever, clinical or biological signs of rejection	at Month 1 after injection

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon
• Investigators: Principal Investigator: Laure HEES, MD, Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): January 1, 2021

Study Registration Dates

• First Submitted: May 31, 2017
• First Submitted That Met QC Criteria: June 6, 2017
• First Posted (Actual): June 8, 2017

Study Record Updates

• Last Update Posted (Actual): July 26, 2018
• Last Update Submitted That Met QC Criteria: July 25, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: solid transplant; grafted children; vaccine recommendation; immunization efficacy; solid grafted children; solid transplant candidate children
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: 69HCL17_0354; 2015-A00854-45 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No